Continuum Modelling of In Vitro Tissue Engineering: A Review - Computational Modeling in Tissue Engineering - page 226

(a) (b)

Fig. 1 a A rotating bioreactor system comprising a cylindrical vessel of diameter L and depth h
rotating about its longitudinal axis, which contains a porous cell-seeded scaffold immersed in
culture medium. Upper figure is a face-on view of the bioreactor. Lower figure is a side view
showing the small gaps between the scaffold and the bioreactor walls. b The perfusion/
compression bioreactor system of El-Haj et al. ( 1990 ), comprising a cell-seeded scaffold
contained within a cylindrical vessel and constrained by a perforated piston, through which
culture medium is perfused via a peristaltic pump. The perforations in the face of the piston
allows simultaneous perfusion and compression of the scaffold

construct are reduced. In the rotating wall bioreactor, the rotation speed determines
the mechanical environment of the cells (and the mass transfer characteristics of
the system); here, the fluid shear stress experienced by the cells may be controlled
by varying the perfusion rate. Indeed this type of bioreactor is frequently employed
in the generation of bone tissue constructs, due to the sensitivity of such cells to
stimulation by fluid shear stress (McCoy and O'Brien 2010 ). A modified perfusion
bioreactor system is employed by El-Haj et al. ( 1990 ), in which cells seeded in a
porous scaffold are subjected to perfusion with media and direct compression
using a piston. This system is illustrated in Fig. 1 b.
The above bioreactors provide convenient model systems with which to
investigate aspects of tissue growth modelling relevant to tissue engineering
applications. Outstanding problems that need to be addressed in order to optimise
the culture environment in these bioreactors include the following

1. How can diffusion-limited mass-transfer limitations be overcome?
2. How do the culture medium, cells and scaffold and other extracellular materials
interact to produce a viable tissue construct?
3. What influence does the mechanical stimulation and biochemical environment
provided by the bioreactor have on tissue growth?

The models that we review in the remainder of this chapter illustrate how
mathematical models can be used to address these questions and, in so doing,
improve the efficiency of cell culture systems.